Acute hypoxia inhibits the increase in oxygen consumption and thermogenesis in the neonatal mammal exposed to cold. Free fatty acids (FFA) and carbohydrate are the major fuel sources for thermogenesis. As fuel sources with severe hypoxia and increased anaerobic glycolysis, the importance of FFA decreases while that of carbohydrate increases. Although mobilization and utilization of these fuels are crucial to heat production, little is known concerning their alterations in the hypoxic cold-stressed neonate. Anaerobic glycolysis is an inefficient generator of ATP, the basic energy source. Cyclic AMP, formed from ATP, is thought to be the "second messenger" linking increased circulating catecholamine levels, lipolysis, and glycogenolysis. Should ATP and cyclic AMP levels be depressed with hypoxia, then fuel mobilization resulting from cold exposure and norepinephrine release might be impaired. Insulin release is suppressed in the hypoxic puppy. The regulatory function of insulin in carbohydrate and lipid metabolism indicates the need for clarification of the importance of low insulin levels to the hypoxic neonate. The specific aims of this investigation are to define a) the roles of ATP and cyclic AMP in the inhibition of fuel mobilization and heat production in the cold-exposed, hypoxic puppy, b) the relative importance of change in FFA and carbohydrate turnover caused by hypoxia in the cold-stressed puppy, and c) the importance of inhibited insulin release to glucose turnover and heat production in the oxygen-deficient puppy. The long-term goals are to define metabolic adjustments in the cold-stressed, hypoxic neonate, and to extrapolate the findings for use in the medical care of the hypoxic infant.